Affectors of Laboratory Results: Part IV

In our discussion of different factors that can result in errors being reported by analytical laboratories, Part IV of our series will address the handling of liquids. I must mention that all this also applies to manipulations of liquids used during compounding. We will look at different characteristics of liquids, namely their solvent and miscibility properties, their evaporation and their viscosity.

Liquids are often involved in several different steps in sample handling and preparation for analysis. If the sample being analyzed is a solid, then it frequently must be dissolved in a suitable solvent. If the sample is a liquid and a second liquid is used for dilution, it must be miscible with the sample, otherwise one will not obtain a diluted sample as the sample will be partially separated from the second liquid. If an extraction step is necessary, a suitable extracting solvent must be selected. In many cases, the extracting solvent is subsequently removed so one with a proper vapor pressure is often selected to minimize the wait-time for evaporation/drying to occur. As discussed last week, it is important to select an extracting solvent that will remove the drug (analyte) as completely as possible and not entrap the drug in the sample matrix so it is unavailable for extraction.

If the sample solution is then analyzed using a method such as high performance/pressure liquid chromatography (HPLC), the solvent used for the sample must be miscible with the mobile phase. In fact, oftentimes the mobile phase can be used as the sample solvent; if gas chromatography (GC) is used, the sample must volatilize rapidly so it will not interfere with the volatilization of the sample itself and result in a poorly shaped peak. If a spectroscopic method is used, the solvent should not have any absorption characteristics at the wavelength of interest. It that is unavoidable, the proper use of solvent blanks or reference samples is important.

Liquid handling is also affected by the evaporation and volatility of the sample. If a sample is prepared and setting on the laboratory bench, it is possible for a portion of the solvent to evaporate and result in a higher-than-actual test result, i.e., an error, being reported, unless an internal standard method of analysis is used. Not knowing whether an internal or external method of analysis is used can place one at a disadvantage; this is another reason why it is necessary to know the complete method utilized when reviewing laboratory results that are reported in the media, etc.

Another variable is viscosity. Viscosity affects �intake� and �delivery� in a measuring device. When using pipettes, etc., viscous liquid flows into the pipette slower than that of a less viscous liquid. If sufficient time is not allowed by the operator for the liquid to completely fill the device, then insufficient liquid (sample) may be obtained for analysis, resulting in a lower-than-actual result, i.e., an error. We are all familiar with what happens when a viscous liquid such as glycerin is placed in a cylindrical graduate for measuring and then we pour the glycerin into the next receptacle; it takes a long time for the glycerin to be delivered from the graduate. If a viscous liquid is used in the analytical process and insufficient time is allowed for delivery, there will be insufficient liquid obtained for the analytical procedure, possibly resulting in an error.

Another comment on the use of pipettes, one must make sure they know which type of pipettes are being used; TD=To deliver, TC=To contain; a TD pipette should not be �blown out� but a TC pipette should be. When micropipettes are being used, clean, new tips should be used for each sample. The tips should be placed on the micropipette very firmly. A smooth action should be used to withdraw the sample and a smooth action should be used to deliver the sample and sufficient time allowed for all the sample to be removed. When tips are re-used, they sometimes have a tendency to introduce an error because in the next operation, not all the sample may be delivered and with re-use, this error may increase because new sample is introduced and not all delivered. Pipettes must be routinely calibrated.

In summary, laboratories must have complete Standard Operating Procedures addressing these issues and when critical analyses are reported in the media, it is very important to be assured of the competency and adherence to Good Laboratory Practices by the laboratory doing the analytical work.

Next week, we will discuss standards (primary and secondary) and USP Reference Standards used by laboratories in establishing standard curves for the analysis, followed by the difference between internal standards and external standards and how these can affect reported laboratory results.

Loyd V. Allen, Jr., Ph.D., R.Ph
Editor-in-Chief

If you are looking for any of these items and much more look no further than IJPC�s Compounder�s Network Listserv. It�s where nearly 1000 compounders in 60 different countries come to chat. Just this week pharmacists on the listserv discussed:

• Ketamine oral or nasal
• Volume of Water Retainer by a Filter
• Antibiotics in PLO
• Night Sweats
• BIO HRT Counseling
• Aloe Vera
• Insurance

Here are a few of the abstracts added to CompoundingToday.com�s literature search this week. All abstracts relate to hormone replacement therapy.

The easiest way to find more abstracts on this topic is to click �Compounding Article Search� from CT.com�s homepage and then select �Hormone Replacement Therapy� from the pull down menu on the �Select Topic� option. The following is just a sampling of some new ones added.

• Fugate SE, Church CO. Nonestrogen treatment modalities for vasomotor symptoms associated with menopause. Ann Pharmacother 2004; 38(9): 1482-1499.
• Huntley AL, Ernst E. A systematic review of herbal medicinal products for the treatment of menopausal symptoms. Menopause 2003; 10(5): 465-476.
• Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EH, Aleman A, Lampe JW, van der Schouw YT. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. JAMA 2004; 292(1): 65-74.
• Kronenberg F, Fugh-Berman A. Complementary and alternative medicine for menopausal symptoms: A review of randomized, controlled trials. Ann Intern Med 2002; 137(10): 805-813.
• Sicat BL, Brokaw DK. Nonhormonal alternatives for the treatment of hot flashes. Pharmacotherapy 2004; 24(1): 79-93.

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